55301-19-4Relevant academic research and scientific papers
Mediators of hedgehog signaling pathways, compositions and uses related thereto
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, (2015/11/27)
The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function by contacting the cell with a hedgehog antagonist, such as a small molecule, in a sufficient amount to aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize hedgehog activity.
Potent inhibitors of the Hedgehog signaling pathway
Brunton, Shirley A.,Stibbard, John H. A.,Rubin, Lee L.,Kruse, Lawrence I.,Guicherit, Oivin M.,Boyd, Edward A.,Price, Steven
, p. 1108 - 1110 (2008/09/19)
A small family of phenyl quinazolinone ureas is reported as potent modulators of Hedgehog protein function. Preliminary SAR studies of the urea substituent led to a nanomolar Hedgehog antagonist.
Mediators of hedgehog signaling pathways, compositions and uses related thereto
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, (2008/06/13)
The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function by contacting the cell with a hedgehog antagonist, such as a small molecule, in a sufficient amount to aberrant growt
Novel nonpeptide CCK-B antagonists: Design and development of quinazolinone derivatives as potent, selective, and orally active CCK-B antagonists
Padia, Janak K.,Field, Mark,Hinton, Joanna,Meecham, Ken,Pablo, Julius,Pinnock, Rob,Roth, Bruce D.,Singh, Lakhbir,Suman-Chauhan, Nirmala,Trivedi, Bharat K.,Webdale, Louise
, p. 1042 - 1049 (2007/10/03)
We have designed a novel series of CCK-B receptor antagonists by combining key pharmacophores, an arylurea moiety of 1 and a quinazolinone ring of 3, from two known series. Our earlier studies showed that compounds with methylene linkers in our 'target' produced moderate binding affinity and selectivity for CCK-B receptors, whereas its higher and lower homologues resulted in loss of affinity. Introduction of -NH- as a linker dramatically enhanced binding affinity and selectivity for CCK-B receptors, thus providing several compounds with single-digit nanomolar binding affinity and excellent selectivity. Analogous to the earlier studies of the series of quinazolinone derivatives 3, we also found 3-isopropoxyphenyl as a preferred substitution on the N-3 quinazolinone. Electron-withdrawing substitutions on the urea terminal phenyl ring enhanced the CCK-B potency. Representative compounds of this series were tested in the functional assay and showed pure antagonist profiles. Compounds 51 and 61 were orally active in the elevated rat X-maze test. These compounds were also evaluated for their pharmacokinetic profile. The absolute oral bioavailability of compound 61 was 22% in rats.
Design and synthesis of novel nonpeptide CCK-B receptor antagonists
Padia,Chilvers,Daum,Pinnock,Suman-Chauhan,Webdale,Trivedi
, p. 805 - 810 (2007/10/03)
A novel hybrid series of nonpeptide CCK-B receptor antagonists has been designed from two known series derived from asperlicin. An efficient synthesis of 2-aminoquinazolinone, an intermediate for the synthesis of a targeted analog, has been developed.
A Synthetic Approach to Peptides of o- and p-Aminobenzoic Acids
Stewart, Frederick H. C.
, p. 1629 - 1638 (2007/10/02)
Active esters of o- and p-aminobenzoic acids served as coupling components syntheses without concomitant protection of the relatively inert aromatic amino group.The products were then treated directly with benzyloxycarbonylamino acid symmetrical anhydrides to form higher peptide derivatives.An analogue of leucine-enkephalin with the glycyglycyl segment replaced by a p-aminobenzoyl residue has been synthesized by this route.
